This project uses a multidisciplinary approach to study tumor cell biology, so as to further our understanding of the basic nature of human malignancy, and to develop techniques for early detection and treatment. Our major effort is a genetic analysis of malignancy using somatic cell hybrids, and tumor virology. Interspecific hybrid cells are formed by cell fusion and analyzed by isozymes chromosome banding, and then tested for properties related to malignancy. These include: RNA tumor virus replication, spontaneous and induced expression of covert genomes, viral receptors, host range and biohazard potential, detection of virogenes by molecular hybridization, expression and regulation of cell and virion DNA polymerase, chromosome segregation, growth in nude mice, contact inhibition, expression of differentiated function, carcinogen metabolism including aryl hydrocarbon hydroxylase, and tumor antigens with immunotherapy trials. Correlation of chromosome content with these properties allows identification and subsequent gene assignment. Other areas include growth of human tumors in nude mice for cell kinetic and therapy trials, and studies of tumor blood flow and perfusion in experimental tumors. BIBLIOGRAPHIC REFERENCES: Brown, S., Wiebel, F.J., Gelboin, H.V., Minna, J.D.: Assignment of a Locus Required for Flavoprotein-linked Mono-oxygenase Expression to Human Chromosome 2. Proc. Natol. Acad. Sci. USA 73: 4628-4632, 1976. Cohen, M.H., Strauss, B.L. Enhancement of the antitumor effect of 1,3-bis (2-chloroethyl)-nitrosourea (BCNU) by phenylethyl-biguanide (phenormin). Oncology 33: 257-259, 1977.